Van beleggers
voor beleggers
Uitgebreid zoeken

Beurscodes, betekenis en hulp bij zoeken

Europa

AEX
Euronext Amsterdam
BRU
Euronext Brussels
PSE
Euronext Paris
LIS
Euronext Lissabon
CHX
CBOE Europe, grote(re) EU aandelen
NAV
Investment Funds (NAV)

Noord-Amerika

NYS
New York Stock Exchange
OTC
CBOE BZX Exchange (US)
TSE
Toronto Stock Exchange

Kunt u een instrument niet vinden?

Zoek dan via de zogenaamde ISIN code. Elk instrument, aandeel etc. heeft een unieke code.

Kies vervolgens - wanneer er meerdere resultaten zijn - de notering op de beurs van uw keuze.

Waar vind ik die ISIN code?

Google de naam van het instrument, aandeel etc. met de toevoeging 'ISIN'.

Als zoeken op ISIN code geen resultaten oplevert hebben wij het instrument of aandeel niet in onze koersendatabase.

desktop iconMarkt Monitor
Home  /  Forum  /  Galapagos  /  GLPG4716

Ontvang nu dagelijks onze kooptips!

word abonnee

Aandeel Galapagos AEX:GLPG.NL, BE0003818359

  • 27,700 16 apr 2024 17:36
  • -0,440 (-1,56%) Dagrange 27,620 - 27,960
  • 82.849 Gem. (3M) 80,1K

GLPG4716

55 Posts
Pagina: 1 2 3 »» | Laatste | Omlaag ↓
  1. Lama Daila 7 november 2020 13:03
    GLPG4716 was al vermeld onder het draadje “nieuwe fibrosis compounds”, maar aangezien het al naar fase2 gaat verdient het wel zijn eigen draadje.

    GLPG4716 is OATD-01 van OncoArendi.

    www.glpg.com/IPF

    GLPG4716
    Lung diseases like IPF are associated with an increased chitinase activity, which strongly correlates with disease stage, progression and prognosis. Chitinases (predominantly CHIT1) are involved in macrophage activation. Inhibition of chitinase activity translates into a potential therapeutic benefit, as shown in a range of preclinical models. GLPG4716 has shown robust anti-fibrotic activity in multiple animal models, when compared with the standard of care.

    GLPG4716 (formerly OATD-01 inlicensed from OncoArendi) is a novel, small molecule CHIT1/AMCase inhibitor targeting a key pathway in tissue remodeling. It has shown compelling translational data, a favorable profile in animal studies at expected therapeutic doses and it has successfully completed Phase 1 studies in healthy volunteers. Galapagos aims to bring GLPG4716 to a Phase 2 clinical trial for the treatment of IPF and possibly other diseases with a fibrotic component.

  3. Lama Daila 7 november 2020 13:06
    Tijdens de conference call 3Q20 gaf Andre volgende toelichting:

    seekingalpha.com/article/4386233-gala...

    Andre Hoekema

    Thank you, Onno. Good afternoon everybody. In our presentations, we often speak about our internal pipeline and here I would like to highlight how we also add external assets. There're actually two reasons to do that. First of all, we have a very strong balance sheet and we really want to use that not only to grow our internal pipeline and accelerate programs through the clinic, but actually also add external assets to our R&D engine.

    And talking about the engine, both in discovery and in clinical, we have a lot of expertise that engine really fire on all cylinders. So in our view, it really makes a lot of sense to not only use it for internal molecules, but also add more tools from third party stuff that we think really makes sense.

    Of course, in that effort we’re really focused on inflammation and fibrosis, the core indication areas of the Company and it will not surprise you that when we talk about criteria, we really look for molecules that really fit Galapagos that means multiple modes of action high-risk high-reward. And in that way, they should strengthen our pipeline.

    On the next slide, you actually see the deals that we have since signed this year. We signed a number of deals with molecules that hit all those criteria, Fibrocor and Scipher both from North America, Canada and Boston. Just a few words about it, Fibrocor has come up with noble targets in fibrosis based on patient samples, very complimentary to what we do. And we've moved to the first program that we licensed in Fibrocor to a candidate drug, so very pleased with that.

    And Scipher, it's some similar complimentary technologies operating from Boston. They identify target targets based on the molecular signature in patients. We think that also fits very well with our own internal programs. In Ryvu, identified a novel inflammation targets that we really liked companies are located in Krakow, Poland, because we've seen a deal. And today, I'm really pleased to say a few words about the first clinical phase efforts that we licensed from companies, also in Poland, in Warsaw in fibrosis.

    So, let me first say a few words about the business deal. It's a collaboration on a really novel class of fibrosis targets, and currently getting ready some breakthrough work in public in this target class, chitinase and chitinase play a role in fibrotic diseases and mostly in lungs so that really fits with interest.

    We have a fibrosis franchise under ways which really [indiscernible] 1205 on earlier programs and we really think there's a very nice niche where we can add another program. So, we decided to work with OncoArendi. You see the deal structure, an upfront 25 million development, regulatory sales milestones for a total of 220 million cost of royalties. We also negotiated the right to get access to other chitinase programs in case those fit in candidate as well.

    So, let me say a few words about this novel target class. Chitinase are known to play a role in lung fibrosis and it is a very novel class. But at the same time, we'd like it because there's quite a bit of elevation. In knockout mice, you see that mice line that chitinase shows a very reduced disease burden in IPF models, and moreover, the molecule that OncoArendi has in development OATD-01 in those two mice and they really reduced the disease burden.

    So the tech class to chitinase, as I said, very well validated, we are not aware of any competition. So, typically go off first in class potential. We think there's really a lot of room to bring us into IPF and possibly other fibrosis disorders. And at this point, the Piet and Walid are preparing a Phase 2b study to bring this molecule forward.

    So, if I can have the next slide, just a bit of detail on the elevation that I just mentioned. Here you see some data that show what bleomycin, which is the standard animal model for IPF. Just on the left to control if you see healthy mice. On bleomycin treatment, you get a formation of lesions in the lungs, expressed by Ashcroft score.

    And as you can see, the molecule from OncoArendi really reduces that net effect similar to the syndrome. So, this is one of the validations that I talked about. And we're really excited about clinical asset that fits in right behind ziritaxestat, which is in a large Phase 3 study, as you all know, and troubled by where we report the Phase 2 data shortly. So, in summary, I am very happy to be adding this asset to our pipeline.
  4. Lama Daila 7 november 2020 13:10
    OncoArendi heeft onlangs nog gepubliceerd dat OATD-01 ook inzetbaar zou kunnen zijn in NASH.
    In de slides van de deal staat ook “potential for other diseases with a fibrotic component”, waar NASH volgens mij wel onder hoort.

    oncoarendi.com/en/oncoarendi-therapeu...

    OncoArendi Therapeutics expands the therapeutic potential of its Chitinase Platform
    October 13, 2020
    OncoArendi develops OATD-01 as a drug candidate for treatment of severe inflammatory and fibrotic diseases. Clinical trials in patients must be preceded by a number of preclinical safety studies, including GLP standard chronic toxicology. Such studies, outsourced to Charles River (USA), a leading global CRO (Contract Research Organization) have recently completed dosing. The 6 and 9 month period of administration of OATD-01 in rats and dogs (respectively) has just ended. A recovery phase of several weeks is currently ongoing. Preliminary reports of these studies are expected at the end of January 2021, while the final reports will be obtained in the second half of 2021. It should be emphasized that previously completed 17-week toxicology studies, also performed by Charles River, already enable Phase IIa studies in sarcoidosis patients to begin early next year.

    “Successful completion of the 6 and 9 month toxicology studies may enable future administration of OATD-01 for indefinite periods of time to patients in diseases, in which blocking of the therapeutic target (chitinases) by the OATD-01 may have a therapeutic effect. One such widespread and as of today uncurable diseases that affects tens of millions of people worldwide is nonalcoholic steatohepatitis (NASH)” – said Dr Rafal Kaminski, Board Member and Chief Scientific Officer, OncoArendi Therapeutics S.A.

    OncoArendi has just received new and very exciting results from a preclinical study conducted by Sanyal Biotechnology (USA), a CRO working with a number of leading pharmaceutical companies developing therapies for NASH. The results obtained in the mouse model (DIAMONDTM) clearly indicate that OATD-01 has demonstrated a therapeutic effect by statistically significant reduction of a number of parameters of the disease. Similar effects were observed with another lead compound that shares the same mechanism of action as OATD-01. The results obtained in this model are an independent confirmation of the therapeutic efficacy of OATD-01, observed previously in another mouse model of NASH (STAMTM) by SMC Laboratories in Japan. The convergence and statistical significance of the two experiments highlights the potential of OATD-01 and other chitinase inhibitors in treatment of NASH.

    Positive results from both NASH models and the completion of 6-9 month toxicology studies build value and significantly expand the therapeutic potential of compounds developed in the OncoArendi’s flagship Chitinase Platform.
  5. Lama Daila 7 november 2020 13:15
    OncoArendi is trots op de resultaten en publicaties rond OATD-01 (=GLPG4716).
    Op Twitter schrijven ze het volgende:
    OATD-01 recognized as one of the 55 most promising drug candidates in the last 15 years!
    Reviewers and Editors of the Journal of Medicinal Chemistry have recommended publication of this OncoArendi article in its prestigious Drug Annotations series: lnkd.in/eie8ntC
    Only the most promising drugs for treating human diseases are featured there.

    oncoarendi.com/en/american-journal-of...

    American Journal of Medicinal Chemistry distinguishes OncoArendi publication on OATD-01
    October 21, 2020
    A new publication about the discovery and preclinical characterization of OATD-01, authored by the scientists from OncoArendi Therapeutics, has just been accepted by the Journal of Medicinal Chemistry (J. Med. Chem). OATD-01 is a first-in-class chitinase inhibitor, which had recently completed Phase I studies and continues its development as a clinical candidate for the treatment of sarcoidosis, idiopathic pulmonary fibrosis (IPF), and possibly other fibrotic and inflammatory diseases.

    The publication describes the drug discovery program that led to the identification of OATD-01. The elements of the medicinal chemistry design, pharmacokinetics and pharmacological properties of the compound are further described in more detail, along with preclinical proof-of-concept data in a model of IPF. These experiments have been performed in-house and by a specialized Japanese CRO.

    The Journal of Medicinal Chemistry is undoubtedly one of the top scientific periodicals in the field of small molecule drug discovery. The Drug Annotations series launched by the journal is intended to showcase the most important and highly innovative compounds that have the biggest potential to make a significant impact on the treatment of human diseases. Since the inception of The Drug Annotations Series over 15 years ago, only 55 compounds have received such distinction. Therefore, OncoArendi Therapeutics is very proud that the discovery and development of OATD-01 has been selected by editor Wendy Young, PhD (Senior VP, Small Molecule Drug Discovery, Genentech) to this very prestigious and highly esteemed series of articles.

    “This publication is a very important milestone for OncoArendi Therapeutics, which documents not only great science, but above all, great drug discovery work with quality that is on par with leading pharma companies. This publication will make OncoArendi an even more established player in the global biotech scene and strongly mark our leadership position in the field of chitinase inhibitors” – said Dr Rafal Kaminski, Chief Scientific Officer, OncoArendi Therapeutics.

    “The data published in this article is a result of several years of hard work and dedication of talented scientists and collaborators of OncoArendi. I would like to thank them all for their passion and efforts, which were recognized by the journal Editors who selected our manuscript for such a high-profile series.” – said Dr Adam Golebiowski, senior corresponding author and one of the co-founders of OncoArendi Therapeutics.

    The research that led to this publication has been co-cofinanced by the National Center for Research and Development (NCBR) in grants, POIR.01.01.01-00-0551/15 (“Development of a first-in-class small molecule drug candidate for treatment of idiopathic pulmonary fibrosis through chitotriosidase inhibition”) and by the National Institutes of Health (NIH) in SBIR grant no 1 R44 HL132721-01 – NHLBI/ NIH (“Development of an Oral Acidic Mammalian Chitinase Inhibitor to Treat Asthma”).

    Publication is now available at: pubs.acs.org/doi/10.1021/acs.jmedchem...

  9. Lama Daila 7 november 2020 14:48
    OncoArendi heeft ook een samenwerking met VIB (Prof. Bart Lambrecht, Gent) rond onderzoek van de rol van de chitinase familie als mogelijke targets voor de behandeling van COVID19-patiënten:

    OncoArendi Therapeutics broadens its collaboration with VIB, a leading life science research institute in Europe, to investigate the role of chitinase family of proteins as potential therapeutic targets in COVID-19 patients

    oncoarendi.com/en/oncoarendi-therapeu...

  10. Lama Daila 7 november 2020 14:58
    Finaal rapport van de resultaten van OATD-01 (= GLPG4716) na de fase1b studie.
    Opvallend is dat OncoArendi van plan was om in 1Q21 eerst een studie op te starten in sarcoidosis patiënten.

    “In Q1 of 2021 the company plans to file for an approval of the next phase clinical trial in sarcoidosis patients”

    oncoarendi.com/en/oncoarendi-therapeu...

    Meer over Sarcoidose:
    sarcoidose.nl/over-sarcoidose/

    Dus toch een heel andere ziekte dan IPF, alhoewel ook longsarcoidose bestaat:
    sarcoidose.nl/over-sarcoidose/vormen-...

    “We expect that in the first half of 2022 we will be able to commence the second part of the study consisting of a longer administration of the drug candidate to another group of patients “

    Die andere groep zal dan vermoedelijk IPF zijn. Dus initiële plannen waren eerst in 1Q21 een fase2a in een kleine groep van sarcoidosis patiënten en dan in 1H22 een fase2b studie in IPF.
    Galapagos wil die fase2a studie gewoon skippen en direct naar een fase2b studie gaan in IPF. Ofwel veel vertrouwen in de compound, ofwel een “gok” om snelheid te maken.
  11. forum rang 4 Sir Piet 7 november 2020 22:12
    quote:

    Lama Daila schreef op 7 november 2020 14:48:

    OncoArendi heeft ook een samenwerking met VIB (Prof. Bart Lambrecht, Gent) rond onderzoek van de rol van de chitinase familie als mogelijke targets voor de behandeling van COVID19-patiënten:

    OncoArendi Therapeutics broadens its collaboration with VIB, a leading life science research institute in Europe, to investigate the role of chitinase family of proteins as potential therapeutic targets in COVID-19 patients

    oncoarendi.com/en/oncoarendi-therapeu...

    Begrijp ik het goed dat ze met dit bedrijf bezig zijn met een post Corona medicijn . Zie persbericht van Oncoarendi van 11 september j.l. Samenwerking met VIB. “ This in turn increases the probability of commercializing one or both of our r&d programs by partnering it with a global biopharmaceutical company” wat dus Galapagos is geworden. Nu begrijp ik ook de grote bedragen.
  12. C200 8 november 2020 09:44
    quote:

    Sir Piet schreef op 7 november 2020 22:12:

    [...]
    Begrijp ik het goed dat ze met dit bedrijf bezig zijn met een post Corona medicijn . Zie persbericht van Oncoarendi van 11 september j.l. Samenwerking met VIB. “ This in turn increases the probability of commercializing one or both of our r&d programs by partnering it with a global biopharmaceutical company” wat dus Galapagos is geworden. Nu begrijp ik ook de grote bedragen.
    Klopt Piet:

    De Poolse vertaling is niet altijd even goed maar wel een leuk artikel:

    Het is de grootste transactie op de Poolse biotechnologiemarkt in de geschiedenis. OncoArendi - een bedrijf waarvan Marcin Szumowski de president is, en de grootste aandeelhouder van de rijkste pool, Michal Solowow, tekenden een contract ter waarde van 1,4 miljard PLN. Nee, de koper is niet de Poolse overheid, maar het Belgische bedrijf Galapagos NV - geniet dus voordat je begint te spugen van het gigantische succes van Polen.

    De noteringen van OncoAredni Therapeutics op de beurs van Warschau stegen vrijdagochtend en al 's ochtends waren ze al met ongeveer 190 procent gestegen. vergeleken met de prijs van de sluiting van donderdag.

    De reden voor deze euforie is de informatie dat het bedrijf, waarvan de president en minderheidsaandeelhouder Marcin Szumowski is, de broer van de voormalige minister van gezondheid, een samenwerkingsovereenkomst heeft getekend met het Belgische bedrijf Galapagos, een biotechnologieleider in Europa. De waarde van dit langlopende contract bedraagt ??322 miljoen EUR, ofwel ongeveer 1,4 miljard PLN. Dit is de grootste transactie in de geschiedenis in de biotechnologie-industrie, dus er is genoeg om tevreden over te zijn. Dit is echt een historisch moment voor de Poolse biotech-industrie.

    Waar gaat het contract eigenlijk over?
    Het succes van OncoArendi ligt in de ontwikkeling van chitinase-remmende technologie. Deze omvatten moleculen op basis waarvan het geneesmiddel voor gebruik bij de behandeling m.in . pulmonale fibrose en astma.

    De euforie op de aandelenmarkt wordt bovendien verklaard door het feit dat pulmonale fibrose een van de meest voorkomende complicaties is na COVID-19.

    Het contract, waarbij het Poolse bedrijf in eerste instantie 25 miljoen EUR zal ontvangen, voorziet in de samenwerking van beide bedrijven bij de ontwikkeling van het chitinaseplatform en verleent de Belgische partner een exclusieve licentie voor de verdere klinische ontwikkeling en commercialisering van het OATD 01-molecuul en andere dubbele chitinaseremmers en voor wereldwijde verkoop. De medicijnen die zijn gebaseerd op de technologie ontwikkeld door OncoArendi zullen naar verwachting binnen enkele jaren op de markt komen.

    Het is triest dat we onze prestaties aan buitenlandse handen moeten afstaan

    En in een dergelijke situatie mogen we enerzijds blij zijn dat het Poolse bedrijf wereldwijd grote successen boekt. Aan de andere kant is er echter altijd enige teleurstelling, want om verdere klinische onderzoeken uit te voeren en het medicijn op de markt te brengen, moeten Poolse wetenschappers hun prestaties in het buitenland verkopen.

    Helaas is geen enkel farmaceutisch bedrijf in Polen sterk genoeg om onafhankelijk alle fasen van klinische proeven uit te voeren en te leiden tot commercialisering van wetenschappelijke prestaties. Dus uiteindelijk drinkt iemand anders de room.

    spidersweb.pl/bizblog/miliardowy-kont...
  13. Lama Daila 8 november 2020 09:57
    quote:

    Sir Piet schreef op 7 november 2020 22:12:

    [...]
    Begrijp ik het goed dat ze met dit bedrijf bezig zijn met een post Corona medicijn . Zie persbericht van Oncoarendi van 11 september j.l. Samenwerking met VIB. “ This in turn increases the probability of commercializing one or both of our r&d programs by partnering it with a global biopharmaceutical company” wat dus Galapagos is geworden. Nu begrijp ik ook de grote bedragen.
    Inderdaad,
    “ If CHIT1 inhibitors prove efficacious in these sophisticated mouse models and the translational studies confirm elevated expression of CHIT1 in patients with observed lung fibrosis after COVID-19, OATD-01, a phase II ready drug candidate can potentially be used in a preventing / therapeutic fashion in this population of COVID-19 survivors. ”

  15. Lama Daila 8 november 2020 10:45
    Prof. Bart Lambrecht is al een tijdje bezig met onderzoek naar chitinase in Universiteit Gent:

    De rol van chitinases and chitinase-like eiwitten in type 2 inflammatoire luchtwegaandoeningen (CHITINAIR):
    researchportal.be/nl/project/de-rol-v...

    Ontrafelen van de complexe rol van chitinases in het ontstaan van astma. (3G068319):
    researchportal.be/nl/project/ontrafel...

    De rol van chitinase-achtige eiwitten Ym1 en Ym2 in type 2 immuniteit. (3F011218):
    researchportal.be/nl/project/de-rol-v...

    Mogelijk is dit het project waar OATD-01 ook betrokken is:
    ClinicalTrials.COV : follow up van patienten die meedoen aan interventionele klinische studies naar het gebruik van immunomodulatoren bij ernstige COVID-19 infectie (01C04520):
    researchportal.be/nl/project/clinical...

  16. forum rang 4 Wall Street Trader 8 november 2020 10:51
    OATD-01 is the first-in-class CHIT1 inhibitor, currently completed phase 1b of clinical trials, to be a potential treatment for IPF.

    Chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are the enzymatically active chitinases that have been implicated in the pathology of chronic lung diseases such as asthma and interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis. The clinical and preclinical data suggest that pharmacological inhibition of CHIT1 might represent a novel therapeutic approach in IPF. Structural modification of an advanced lead molecule 3 led to the identification of compound 9 (OATD-01), a highly active CHIT1 inhibitor with both an excellent PK profile in multiple species and selectivity against a panel of other off-targets. OATD-01 given orally once daily in a range of doses between 30 and 100 mg/kg showed significant antifibrotic efficacy in an animal model of bleomycin-induced pulmonary fibrosis.

    Supplementary Data PDF:

    ndownloader.figstatic.com/files/25176484

  18. Loureiro 8 november 2020 11:10
    quote:

    Sir Piet schreef op 8 november 2020 10:58:

    Begrijp ook van de webcast van André Hoekema dat er geen concurrerende middelen voor zover bekend in ontwikkeling zijn.Meteen starten in fase 2b zal het product binnen enkele jaren naar de markt brengen indien succesvol. Is dit een nieuwe verborgen parel?
    Naast Toledo, inderdaad een tweede parel. Volgend jaar wordt het bijgevolg opnieuw heel interessant en spannend.
  19. forum rang 5 Endless 8 november 2020 11:16
    quote:

    Sir Piet schreef op 8 november 2020 10:58:

    Begrijp ook van de webcast van André Hoekema dat er geen concurrerende middelen voor zover bekend in ontwikkeling zijn.Meteen starten in fase 2b zal het product binnen enkele jaren naar de markt brengen indien succesvol. Is dit een nieuwe verborgen parel?
    Ja
  20. forum rang 4 Wall Street Trader 8 november 2020 11:26
    quote:

    Sir Piet schreef op 8 november 2020 10:58:

    Begrijp ook van de webcast van André Hoekema dat er geen concurrerende middelen voor zover bekend in ontwikkeling zijn.Meteen starten in fase 2b zal het product binnen enkele jaren naar de markt brengen indien succesvol. Is dit een nieuwe verborgen parel?
    This asset is a phase II-ready chitotriosidase/ acidic mammalian chitinase (CHIT1/AMCase) inhibitor for the treatment of idiopathic pulmonary fibrosis (IPF) and other diseases with a fibrotic component.

    OncoArendi will receive an upfront payment of EUR 25 Million and will be entitled to milestones payments up to EUR 320 Million.

    On top of that, Galapagos will pay EUR 2 million for the right of first negotiation on any other programmes emerging from OncoArendi’s chitinase platform.

    This is a very good addition to the expanding pipeline of Galapagos!

    It strengthens and complements Galapagos fibrosis portfolio and Galapagos get's access to an innovative pipeline.

    Andre Hoekema, Ph.D. - Chief Business Officer:

    We really look for molecules that really fit Galapagos that means multiple modes of action high-risk high-reward. And in that way, they should strengthen our pipeline.

    License deals strengthen internal pipeline PDF.
    Bijlage:
55 Posts
Pagina: 1 2 3 »» | Laatste |Omhoog ↑

Meedoen aan de discussie?

Word nu gratis lid of log in met je emailadres en wachtwoord.

Direct naar Forum

Premium

Weinig houvast voor beleggers in Galapagos

Het laatste advies leest u als abonnee van IEX Premium

Inloggen Word Abonnee

Galapagos Nieuws

  1. 12 apr KBC Securities verlaagt koersdoel Galapagos naar 50 euro
  2. 05 apr Galapagos toont innovatieve aanpak in hematologische kankerzorg
  3. 23 feb AEX op de waakvlam het weekend in, koersdreun Besi, Alfen en Galapagos 2
  4. 23 feb Beursblik: gebrek aan opwaarts potentieel voor Galapagos op korte termijn
  5. 23 feb Gaat AEX op recordjacht of gaat de beursweek uit als een nachtkaars?
  6. 23 feb Update : Galapagos voldoet aan verwachtingen
  7. 19 feb Beursblik: cashburn belangrijk voor Galapagos
  8. 15 feb Galapagos presenteert nieuwe onderzoeksdata op EBMT-EHA bijeenkomst
  9. 01 feb Galapagos rondt Jyseleca-transactie af
  10. 04 jan Galapagos in zee met Thermo Fisher

Lees verder op het IEX netwerk Let op: Artikelen linken naar andere sites

Gesponsorde links

Meld u aan voor de dagelijkse Beursupdate

Dagelijks een update van het laatste beursnieuws en beleggingskansen in uw mailbox!